Digitalis causes several types of cardiac arrhythmias. These arrhythmias could result from different mechanisms such as an enhanced diastolic depolarization, an increased calcium influx, an increased intracellular calcium concentration, an increased sodium influx or the poisoning of the sodium potassium pump. These mechanisms lead to the development of transient oscillations and of small action potentials in the plateau region. The objective of the proposed research is to investigate the mechanisms of different manifestations of digitalis toxicity. The microelectrode technique will be used to record membrane potentials and control voltage and a force transducer to measure force of contraction. Purkinje fibers isolated from ventricles will be perfused in a tissue bath. The role of the poisoning of the sodium potassium pump in the determination of therapeutic and toxic effects of digitalis will be studied. The therapeutic effect will be judged by an increase in force of contraction; the toxic effect by the decline of force of contraction and by onset of arrhythmias. The function of the pump will be modified by several means and the effects of digitalis explored in the same preparation before and after the pump function has been affected. This different procedure will be carried out under different experimental conditions which are known to affect the onset of digitalis toxicity. For example, spontaneous fibers may behave differently from driven fibers. And the therapeutic action may not involve a poisoning of the pump. Also procedures will be carried out to determine whether the pump contributes to the membrane potential in relation to strophanthidin exposure. Other cardiac tissues will be used as not necessarily all of them respond to digitalis in the same manner.